The ecological impact of a bacterial weapon: microbial interactions and the Type VI secretion system

Abstract

Bacteria inhabit all known ecological niches and establish interactions with organisms from all kingdoms of life. These interactions are mediated by a wide variety of mechanisms and very often involve the secretion of diverse molecules from the bacterial cells. The Type VI secretion system (T6SS) is a bacterial protein secretion system that uses a bacteriophage-like machinery to secrete a diverse array of effectors, usually translocating them directly into neighbouring cells. These effectors display toxic activity in the recipient cell, making the T6SS an effective weapon during inter-bacterial competition and interactions with eukaryotic cells. Over the last two decades, microbiology research has experienced a shift towards using systems-based approaches to study the interactions between diverse organisms and their communities in an ecological context. Here, we focus on this aspect of the T6SS. We consider how our perspective of the T6SS has developed and examine what is currently known about the impact that bacteria deploying the T6SS can have in diverse environments, including niches associated with plants, insects and mammals. We consider how T6SS-mediated interactions can affect host organisms by shaping their microbiota, as well as the diverse interactions that can be established between different microorganisms through the deployment of this versatile secretion system.

Keywords: Type VI secretion system (T6SS); host-pathogen interactions; inter-bacterial competition; microbial interactions; microbiota; sociomicrobiology.

Figure 1.

Structure of the Type VI secretion system (T6SS). The system is represented in its contracted state, after a “firing” event. The cytoplasmic baseplate, housing the VgrG-PAAR spike, docks on the membrane complex and acts as a platform for the assembly of the Hcp tube surrounded by the extended contractile sheath. TssA coordinates assembly and extension of the Hcp tube and sheath. During the firing event, contraction of the sheath propels the Hcp-VgrG-PAAR puncturing structure through the membrane complex, out of the attacking cell and into a neighbouring target cell. After contraction, TssH depolymerizes the sheath, facilitating a new round of T6SS assembly and firing. T6SS effectors (cargo and specialized) decorate the puncturing structure and are released into the target cell. Susceptible target cells suffer the noxious actions of the delivered T6SS effectors, while resistant target cells (e.g. sibling cells) possess cognate immunity proteins that bind to the incoming effectors to neutralise them. Note that a Gram-negative bacterium is depicted for the example of a susceptible cell, but the same general mechanism would apply for susceptible eukaryotic cells. IM, inner membrane; PG, peptidoglycan cell wall; OM, outer membrane.

Figure 2.

Known types of cellular interactions involving the T6SS. (A) The T6SS enables bacteria to outcompete other members of the microbiota by killing them or inhibiting their growth. (B) Effectors secreted by the T6SS (red ellipses) can sequester nutrients present in the environment and facilitate their transport into the secreting cell. (C) Bacteria can deliver T6SS effectors to host cells as a virulence mechanism during colonization. (D) Signalling molecules and metabolites found in the host environment can induce expression of the T6SS in bacteria. (E) Bacteria can use the T6SS to outcompete other members of the microbiota and colonize a niche provided by a host. Subsequently they can use the T6SS to prevent invasion by pathogenic organisms. (F) Members of the microbiota secrete signalling molecules and metabolites that can induce expression of the T6SS in bacteria. (G) Bacteria can use T6SS-delivered effectors to lyse related cells (non-kin); DNA released by this mechanism (black double helix) can then be acquired by the secreting cells. (H) Quorum sensing systems can enable policing of cheater cells by positively controlling the expression of T6SS effector and immunity genes (green boxes following black arrow). (I) Minor differences in T6SS effectors and immunity proteins allow otherwise isogenic cells to differentiate and kill each other. (J) The T6SS allows bacteria to kill microbial eukaryotes that may be competitors and predators. Throughout all panels, green ellipses represent T6SS effectors and green arcs represent T6SS immunity proteins. Panels with a green frame indicate interactions among bacteria only. Panels with red/green frames indicate interactions between bacteria and eukaryotes. Skulls represent cell death or growth inhibition by delivered T6SS effectors.